The mucosal immune systems has evolved to become incredibly flexible. On the one hand it is the first line of defense against pathogens from the external environment and must react quickly to prevent infection. Interestingly the predominant tone of the GI tract is one of suppression or down-regulation of immune responses. This is an active process whose mechanisms have just started to be elucidated. The hallmark of this suppressed state of phenomenon of oral tolerance. This involves the active suppression of systemic immune responses following the initial (ans possibly subsequent) administration of antigen via the oral route. In food allergic patients the presence of hypersensitivity reactions to food antigens, suggests that this tolerant state may have ben altered. Since several components go into the development of tolerance (nature of the antigen, dose of the antigen, genetics, co-administered adjuvants, etc.), any alteration in this process may result in priming and a failure to tolerize. Such may the case in the development of food allergy. It is the goal of this proposal to identify whether oral tolerance exists in patients with various forms of food allergy and, if so, what mechanisms govern the altered responses to food antigens. This will be addressed in three specific aims: #1. Does oral tolerance exist to soluble protein antigens in milk allergic children? #2. What is the nature of the cytokine profile of antigen activated T cells following oral administration of antigen in milk allergic children? #3, Does the presence or absence of oral tolerance correlate with intestinal permeability defects? The results of such studies should provide a basis for a better understanding of the nature of food allergy and potentially provide useful information that will allow us to develop approaches to therapy.